Computational biology seeks to understand complex spatio-temporal phenomena across multiple levels of structural and functional organisation. However, questions raised in this context are difficult to answer without modelling methodologies that are intuitive and approachable for non-expert users. Stochastic rule-based modelling languages such as Kappa have been the focus of recent attention in developing complex biological models that are nevertheless concise, comprehensible, and easily extensible. We look at further developing Kappa, in terms of how we might define complex models in both the spatial and the temporal axes. In defining complex models in space, we address the assumption that the reaction mixture of a Kappa model is homogeneous and well-mixed. We propose evolutions of the current iteration of Spatial Kappa to streamline the process of defining spatial structures for different modelling purposes. We also verify the existing implementation against established results in diffusion and narrow escape, thus laying the foundations for querying a wider range of spatial systems with greater confidence in the accuracy of the results. In defining complex models over time, we draw attention to how non-modelling specialists might define, verify, and analyse rules throughout a rigorous model development process. We propose structured visual methodologies for developing and maintaining knowledge base data structures, incorporating the information needed to construct a Kappa rule-based model. We further extend these methodologies to deal with biological systems defined by the activity of synthetic genetic parts, with the hope of providing tractable operations that allow multiple users to contribute to their development over time according to their area of expertise. Throughout the thesis we pursue the aim of bridging the divide between information sources such as literature and bioinformatics databases and the abstracting decisions inherent in a model. We consider methodologies for automating the construction of spatial models, providing traceable links from source to model element, and updating a model via an iterative and collaborative development process. By providing frameworks for modellers from multiple domains of expertise to work with the language, we reduce the entry barrier and open the field to further questions and new research.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:669358 |
| Date | January 2015 |
| Creators | Wilson-Kanamori, John Roger |
| Contributors | Danos, Vincent; Plotkin, Gordon; Hillston, Jane |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/11687 |
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